Engineered production of cancer targeting peptide (CTP)-containing C-1027 in Streptomyces globisporus and biological evaluation.
Engineered production of cancer targeting peptide (CTP)-containing C-1027 in Streptomyces globisporus and biological evaluation.
复制标题
靶向肽（CTP）的工程生产 - 全球链霉菌和生物学评估中含有C-1027。
DOI：
10.1016/j.bmc.2016.04.017
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发表时间：
2016-09-01
影响因子：
3.5
通讯作者：
Shen B
中科院分区：
文献类型：
--
作者：
Li W;Li X;Huang T;Teng Q;Crnovcic I;Rader C;Shen B
癌症靶向肽（CTP）与小分子治疗剂的缀合已经成为选择性地向癌细胞递送有效（但通常非特异性）细胞毒性剂的有前景的策略。在这里，我们报告了工程生产的CTP（NGR）-含有C-1027和评价其对选定的癌细胞系的活性。C-1027是由球孢链霉菌产生的烯二炔色蛋白，由脱辅基蛋白（CagA）和烯二炔发色团（C-1027）组成。NGR是靶向肿瘤血管系统中的CD 13的CTP。S. globisporus SB 1026是一种经工程改造以编码CagA的重组菌株，其C末端融合有NGR序列，该重组菌株直接产生与天然C-1027具有同等活性的含NGR的C-1027。我们的研究结果证明了通过代谢途径工程和微生物发酵生产含CTP的烯二炔色蛋白的可行性，并将激励人们努力工程化其他含CTP的药物结合蛋白用于靶向递送。
Conjugation of cancer targeting peptides (CTPs) with small molecular therapeutics has emerged as a promising strategy to deliver potent (but typically nonspecific) cytotoxic agents selectively to cancer cells. Here we report the engineered production of a CTP (NGR)-containing C-1027 and evaluation of its activity against selected cancer cell lines. C-1027 is an enediyne chromoprotein produced by Streptomyces globisporus, consisting of an apo-protein (CagA) and an enediyne chromophore (C-1027). NGR is a CTP that targets CD13 in tumor vasculature. S. globisporus SB1026, a recombinant strain engineered to encode CagA with the NGR sequence fused at its C-terminus, directly produces the NGR-containing C-1027 that is equally active as the native C-1027. Our results demonstrate the feasibility to produce CTP-containing enediyne chromoproteins by metabolic pathway engineering and microbial fermentation and will inspire efforts to engineer other CTP-containing drug binding proteins for targeted delivery.